EP0042592B1 - N-Heteroaryl-alkylendiamine, Verfahren zu ihrer Herstellung sowie ihre Verwendung - Google Patents

N-Heteroaryl-alkylendiamine, Verfahren zu ihrer Herstellung sowie ihre Verwendung Download PDF

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Publication number
EP0042592B1
EP0042592B1 EP81104679A EP81104679A EP0042592B1 EP 0042592 B1 EP0042592 B1 EP 0042592B1 EP 81104679 A EP81104679 A EP 81104679A EP 81104679 A EP81104679 A EP 81104679A EP 0042592 B1 EP0042592 B1 EP 0042592B1
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Prior art keywords
general formula
alkyl
compounds
different
indazole
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EP81104679A
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German (de)
English (en)
French (fr)
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EP0042592A1 (de
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Fritz Dr. Wiedemann
Ewald Rieger
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Roche Diagnostics GmbH
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Roche Diagnostics GmbH
Boehringer Mannheim GmbH
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Priority to AT81104679T priority Critical patent/ATE11535T1/de
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C07D215/46—Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
    • C—CHEMISTRY; METALLURGY
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    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
    • C07D219/08—Nitrogen atoms
    • C07D219/10—Nitrogen atoms attached in position 9
    • C07D219/12—Amino-alkylamino radicals attached in position 9
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
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    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/18—One oxygen or sulfur atom
    • C07D231/20—One oxygen atom attached in position 3 or 5
    • C—CHEMISTRY; METALLURGY
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    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/28—Two oxygen or sulfur atoms
    • C07D231/30—Two oxygen or sulfur atoms attached in positions 3 and 5
    • C07D231/32—Oxygen atoms
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    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/38—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
    • C07D231/52—Oxygen atom in position 3 and nitrogen atom in position 5, or vice versa
    • C—CHEMISTRY; METALLURGY
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    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D237/20—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/56—One oxygen atom and one sulfur atom
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
    • C07D239/84—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
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    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
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    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/36—Nitrogen atoms
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    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/32—Nitrogen atom
    • C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
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    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Definitions

  • the present invention relates to new N-heteroarylalkylenediamines of the general formula I, which are valuable intermediates for the preparation of substances which have cardiovascular activity, and to processes for their preparation.
  • the invention furthermore relates to the optically active forms and racemic mixtures of these compounds.
  • the C 1 -C 4 -alkyl groups in the radicals R 1 , R 2 , R 3 , R 4 or R 5 are to be understood as straight-chain or branched groups, such as, for example, methyl, ethyl, isopropyl or butyl.
  • the methyl group is particularly preferred.
  • the new compounds of formula 1 are suitable intermediates for the production of compounds with valuable pharmacological properties, for example for the production of cardiovascular-active compounds as described and claimed in EP-A-42 593.
  • cardiotonically active 1-phenoxy-3- [2- (4-indazolylamino) ethylamino] propane-2- can be obtained from 4- (2-aminoethylamino) indazole (Example 3 of this application) by reaction with phenylglycidyl ether ol (Example 13 of EP-A-42 593) can be obtained.
  • the invention further relates to processes for the preparation of compounds of the general formula I.
  • Reactive radicals Y of the general formulas III and IV include, for example to understand the residues of hydrohalic acids or sulfonic acids, chlorides, bromides, mesyloxy, tosyloxy, methylmercapto and methylsulfonyl groups.
  • the chlorides and bromides are preferred.
  • protecting groups B in the general formula III are suitable as protecting groups B in the general formula III.
  • protective groups are, for example, benzyl groups and the phthaloyl group, which are also particularly preferred and can be removed by hydrogenolysis or hydrazinolysis.
  • the reactions according to variant a can be carried out in an inert solvent such as dimethylformamide or acetonitrile and the addition of a base.
  • the process is preferably carried out in water or in a mixture of water and an alcohol such as ethylene glycol or n-propanol at the reflux temperature.
  • the compounds of the formula I can be obtained directly as salts by the preparation processes or, if desired, converted into salts by processes known per se.
  • Particularly suitable salts are the reaction products with hydrohalic acid, such as hydrochloric acid, or oxalic acid.
  • the starting compound used can be obtained in the following way:
  • Sulfur dioxide to pH 7-8 is introduced into a mixture of 66 ml of ethylenediamine and 146 ml of water, whereupon 13.4 g of 4-hydroxyindazole are added and the mixture is heated to 100-110 ° C. for 1 hour with stirring. After cooling, 300 ml of methanol are added and the salts formed, which are washed with methanol, are filtered off with suction. It is gently concentrated in vacuo to 50-100 ml and the by-product formed (N, N'-bis (indazolyl-4) -ethyldiamine) is sucked off. Then you put with conc. Ammonia alkaline and extracted (1 ox) with methylene chloride, dries the extract and concentrates it to approx. 100 ml.
  • Benzoate colorless crystals, mp. 178-180 ° C (Z.), (from isopropanol).
  • Sulfur dioxide to pH 7 is passed into a solution of 74 g of 1,3-diamino-propane in 150 ml of water, whereupon 13.4 g of 4-hydroxy-indazole are added and the mixture is heated at 100 ° C. for 3 hours. By adding twice the amount of methanol, salts are precipitated, from which one sucks off. The filtrate is concentrated, the oily residue by conc. Ammonia made alkaline, whereupon extracted with methylene chloride. By concentrating the extract, 7.8 g (41% of theory) of gray crystals, mp. 154-163 ° C. are obtained.
  • a mixture of 12.0 g of 5-amino-indazole, 146 g of ethylenediamine sulfite, 146 ml of water and 10 ml of n-propanol is heated to 100 ° C. with stirring for 24 hours. After cooling, it is diluted with 500 ml of methanol. After filtering off the precipitated salts, the filtrate is concentrated, the residue by adding conc. Ammonia made alkaline. It is suctioned off, washed with water and obtained 9.4g (59% of theory) crystals, mp. 150-165 ° C.

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Luminescent Compositions (AREA)
  • Pyrane Compounds (AREA)
  • Mechanical Treatment Of Semiconductor (AREA)
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EP81104679A 1980-06-23 1981-06-19 N-Heteroaryl-alkylendiamine, Verfahren zu ihrer Herstellung sowie ihre Verwendung Expired EP0042592B1 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT81104679T ATE11535T1 (de) 1980-06-23 1981-06-19 N-heteroaryl-alkylendiamine, verfahren zu ihrer herstellung sowie ihre verwendung.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE3023369 1980-06-23
DE19803023369 DE3023369A1 (de) 1980-06-23 1980-06-23 Aryloxypropanolamine, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel

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EP0042592A1 EP0042592A1 (de) 1981-12-30
EP0042592B1 true EP0042592B1 (de) 1985-01-30

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Family Applications (2)

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EP81104679A Expired EP0042592B1 (de) 1980-06-23 1981-06-19 N-Heteroaryl-alkylendiamine, Verfahren zu ihrer Herstellung sowie ihre Verwendung
EP81104680A Expired EP0042593B1 (de) 1980-06-23 1981-06-19 Aryloxypropanolamine, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel

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EP81104680A Expired EP0042593B1 (de) 1980-06-23 1981-06-19 Aryloxypropanolamine, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel

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US (3) US4438128A (enrdf_load_stackoverflow)
EP (2) EP0042592B1 (enrdf_load_stackoverflow)
JP (2) JPS5745144A (enrdf_load_stackoverflow)
AT (2) ATE12492T1 (enrdf_load_stackoverflow)
AU (1) AU540425B2 (enrdf_load_stackoverflow)
CA (1) CA1184188A (enrdf_load_stackoverflow)
CS (2) CS244670B2 (enrdf_load_stackoverflow)
DD (1) DD159771A5 (enrdf_load_stackoverflow)
DE (3) DE3023369A1 (enrdf_load_stackoverflow)
ES (1) ES503175A0 (enrdf_load_stackoverflow)
FI (1) FI80681C (enrdf_load_stackoverflow)
HU (1) HU189514B (enrdf_load_stackoverflow)
IL (1) IL63104A (enrdf_load_stackoverflow)
SU (2) SU1287748A3 (enrdf_load_stackoverflow)
ZA (1) ZA814112B (enrdf_load_stackoverflow)

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TW202210480A (zh) 2019-04-17 2022-03-16 美商基利科學股份有限公司 類鐸受體調節劑之固體形式
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Also Published As

Publication number Publication date
DD159771A5 (de) 1983-04-06
AU7187981A (en) 1982-01-07
HU189514B (en) 1986-07-28
FI80681B (fi) 1990-03-30
ZA814112B (en) 1982-07-28
JPH023778B2 (enrdf_load_stackoverflow) 1990-01-24
DE3168611D1 (en) 1985-03-14
DE3023369A1 (de) 1982-01-14
ES8204725A1 (es) 1982-06-01
CA1184188A (en) 1985-03-19
US4438128A (en) 1984-03-20
EP0042592A1 (de) 1981-12-30
US4608383A (en) 1986-08-26
EP0042593A1 (de) 1981-12-30
EP0042593B1 (de) 1985-04-03
ATE11535T1 (de) 1985-02-15
SU1272976A3 (ru) 1986-11-23
CS449281A2 (en) 1985-09-17
ATE12492T1 (de) 1985-04-15
DE3169658D1 (en) 1985-05-09
JPS5732269A (en) 1982-02-20
IL63104A (en) 1987-07-31
CS244661B2 (en) 1986-08-14
US4507488A (en) 1985-03-26
SU1287748A3 (ru) 1987-01-30
ES503175A0 (es) 1982-06-01
CS244670B2 (en) 1986-08-14
FI811897L (fi) 1981-12-24
CS108082A2 (en) 1985-09-17
AU540425B2 (en) 1984-11-15
FI80681C (fi) 1990-07-10
IL63104A0 (en) 1981-09-13
JPS5745144A (en) 1982-03-13

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